We propose to develop a genetic system for Candida albicans as a useful tool in investigating the biochemical basis of virulence. C. albicans has no known sexual phase. The ploidy is unknown. Recombination is unknown. Our preliminary experiments indicate that some strains are heterozygous (for genes determining synthesis of amino acids, purines, or pyrimidines), and that auxotrophic variants arise by mitotic recombination and segregation. Using mitotic recombination, we will develop marked strains and use these to search for a sexual phase. We will simultaneously develop a genetic system independent of meiosis by the use of: mitotic recombination, induced chromosome loss, and protoplast fusion. We will study the genetic determination of virulence by using: (1) sexual genetics and/or (2) asexual genetics. We will isolate a comprehensive set of auxotrophic variants.